Purpose :
Synaptic interactions between cones and horizontal cells play a key role in the center-surround receptive field organization of the retina. Recent physiological studies suggest that complex feedback systems exist between horizontal cells and cones. Three major feedback mechanisms (1.ephaptic, 2.pH-mediated and 3.GABAergic) have been proposed and studied, however, the functional consequences have not yet fully understood. The purpose of the present study is to evaluate how the each mechanism contributes to the feedback function quantitatively through computer simulation.

Methods :
We constructed a mathematical model of cone-horizontal cell network based on physiological characteristics. We developed a cone model by describing phototransduction mechanism in the outer segment, the membrane ionic currents in the inner segment (Ih, IKv, ICa, IK(Ca), IL) and the synaptic terminal (ICa, ICl(Ca), IL). Horizontal cell is modeled with the ionic currents (IGlu, INa, ICa, IKv, IA, IKa, IL). IGlu is modulated by glutamate released from the cone synaptic terminal. The effects of the ephaptic and pH-mediated feedback were modeled as functions of horizontalcell membrane potential. ICa in the cone synaptic terminal was assumed to be directly modulated by the feedback.

Results :
In simulation, the shift of cone ICa activation-range was reproduced with the combination of the ephaptic and pH-mediated feedback mechanisms. Simulated cone responses to a flash of light showed the characteristic responses such as initial transient hyperpolarization and delayed depolarization similar to those observed experimentally. Those response properties could not be reproduced with a single feedback mechanism.

Conclusions :
The results suggest that both the ephaptic and pH-mediated mechanisms are required in the cone-horizontal cell synapse, i.e., the dynamic characteristics of the cone light responses can not be explained by a single feedback system. The results also suggest the functional roles of each feedback system; ephaptic feedback elicits cone voltage shift in the negative direction and the pH-mediated feedback regulates the amplitude of cone calcium current.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.